Recent studied indicate that loss or mutation of tumor suppressor genes is frequently associated with many types of human cancer. The etiology of these cancers is not completely clear. In the case of mesothelioma, the carcinogenic agent(s) is generally considered to be asbestos fibers. It was, therefore, of interest to examine a relatively large (19) collection of cell lines for loss of expression of the retinoblastoma (Rb) gene or mutation in the p53 gene. Our studies to date suggest that loss of Rb expression is not common in mesothelioma. Protein studies will be performed to confirm this conclusion. The status of the p53 gene in mesothelioma is being studied by immunocytochemistry and direct sequencing. To date only 10% (2120) of tumors show mutations, while 3/20 show protein staining higher than normal mesothelial cells. None of the tumors positive for p53 mutations have mutations in Ki-ras codon 61. Examination of expression of platelet-derived growth factor (PDGF)-A chain in tumors retrieved after inoculation of athymic nude mice with derivatives of the immortalized human mesothelial cell MET-5A showed that tumors from PDGF-A chain transfectants but not EJ-ras transfectants overexpressed PDGF-A chain from the endogenous gene. Interestingly, rare tumors from control plasmid transfected cells also overexpressed the endogenous PDGF-A chain gene, suggesting that this may be a common alteration correlating with tumorigenic progression.